Investigation of the role of a novel regulator of insulin secretion

• Project/Area Number: 15K19513
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Kyoto University
• Principal Investigator: Nishi Kiyoto 京都大学, 医学研究科, 医員 (30749362)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: インスリン / 糖代謝 / エネルギー代謝 / 転写調節 / ナルディライジン

Outline of Final Research Achievements

Type 2 diabetes (T2D) is characterized by impaired insulin secretion from pancreatic beta-cells and insulin resistance of the target tissues, such as liver, adipose tissue and muscles.
We analysed NRDC (N-arginine dibasic convertase; Nardilysin)-deficient mice and found that NRDC controls both insulin secretion and insulin sensitivity. Then, we generated organ-specific (pancreatic beta-cell, liver and adipose tissue) NRDC-deficient mice and found that (1) NRDC regulates pancreatic beta-cell function and identity, (2) NRDC regulates insulin sensitivity in both liver and adipose tissue. Part of these results was published in “Diabetes” journal.

Research Products

• [Journal Article] Nardilysin promotes hepatocellular carcinoma through activation of signal transducer and activator of transcription 3 (2017)
  • Author(s): Kasai Y, Toriguchi K, *Hatano E, Nishi K, Ohno M, Yoh T, Fukuyaman K, Nishio T, Okuno M, Iwaisako K, Seo S, Taura K, Kurokawa M, Kunichika M, Uemoto S, *Nishi E
  • Journal Title: Cancer Sci. Volume: 108 Issue: 5 Pages: 910-917
  • DOI: 10.1111/cas.13204
  • NAID: 120006333898
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Nardilysin is required for maintaining pancreatic β-Cell Function. (2016)
  • Author(s): Nishi K, Sato Y, Ohno M, Hiraoka Y, Saijo S, Sakamoto J, Chen P-M, Morita Y, Matsuda S, Iwasaki K, Sugizaki K, Harada N, Mukumoto Y, Kiyonari H, Furuyama K, Kawaguchi Y, Uemoto S, Kita T, Inagaki N, Kimura T and Nishi E
  • Journal Title: Diabetes Volume: 65 Issue: 10 Pages: 3015-3027
  • DOI: 10.2337/db16-0178
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Nardilysin Critically Regulates Insulin Secretion and Glucose Metabolism (2017)
  • Author(s): Nishi K, Ohno M, Saijo S, Morita Y, Matsuda S, Sakamoto J, Chen P, Kimura T, Nishi E.
  • Organizer: 第81回日本循環器学会学術集会
  • Place of Presentation: 金沢
  • Year and Date: 2017-03-17
• [Presentation] Nardilysin Regulates Glucose Homeostasis via the Maintenance of Pancreatic β-Cell Function and Identity (2016)
  • Author(s): 西清人、佐藤雄一、大野美紀子、平岡義範、西城さやか、坂本二郎、陳博敏、森田雄介、松田真太郎、北徹、稲垣暢也、木村剛、西 英一郎
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-11-30
• [Presentation] ナルディライジンによる膵β細胞機能・分化制御機構の解明 (2016)
  • Author(s): 西清人、大野美紀子、西城さやか、森田雄介、松田真太郎、稲垣暢也、西英一郎
  • Organizer: 第37日本肥満学会
  • Place of Presentation: 東京
  • Year and Date: 2016-10-07
• [Presentation] Nardylisin regulates glucose metabolism through insulin secretion (2016)
  • Author(s): 西清人、稲垣暢也、西英一郎
  • Organizer: 第21回アディポサイエンス・シンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 2016-08-20
• [Presentation] Nardilysin is essential for the maintenance of pancreatic β-Cell function and identity (2015)
  • Author(s): Kiyoto Nishi
  • Organizer: 第38回日本分子生物学会年会
  • Place of Presentation: 神戸、日本
  • Year and Date: 2015-12-01
• [Presentation] Nardilysin is Required for Maintaining Function and Identity of Pancreatic β-Cells (2015)
  • Author(s): Kiyoto Nishi
  • Organizer: Keystone symposia “Diabetes: New Insights into Molecular Mechanisms and Therapeutic Strategies (T2)”
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2015-10-25
  • Int'l Joint Research
• [Presentation] Nardilysin is a Critical Regulator of Pancreatic β-Cell Function (2015)
  • Author(s): Kiyoto Nishi
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪、日本
  • Year and Date: 2015-04-24
• [Remarks] 血糖調節の新たなメカニズムの解明（京都大学ニュースリリース）
  • URL: http://www.kyoto-u.ac.jp/ja/research/research_results/2016/160630_1.html